The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
A Central Role for Neuronal AMP-Activated Protein Kinase (AMPK) and Mammalian Target of Rapamycin (mTOR) in High-Protein Diet–Induced Weight Loss
Abstract
OBJECTIVE—A high-protein diet (HPD) is known to promote the reduction of body fat, but the mechanisms underlying this change are unclear. AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) function as majors regulators of cellular metabolism that respond to changes in energy status, and recent data demonstrated that they also play a critical role in systemic energy balance. Here, we sought to determine whether the response of the AMPK and mTOR pathways could contribute to the molecular effects of an HPD. RESEARCH DESIGN AND METHODS—Western blotting, confocal microscopy, chromatography, light microscopy, and RT-PCR assays were combined to explore the anorexigenic effects of an HPD. RESULTS—An HPD reduced food intake and induced weight loss in both normal rats and ob/ob mice. The intracerebroventricular administration of leucine reduced food intake, and the magnitude of weight loss and reduction of food intake in a leucine-supplemented diet are similar to that achieved by HPD in normal rats and in ob/ob mice, suggesting that leucine is a major component of the effects of an HPD. Leucine and HPD decrease AMPK and increase mTOR activity in the hypothalamus, leading to inhibition of neuropeptide Y and stimulation of pro-opiomelanocortin expression. Consistent with a cross-regulation between AMPK and mTOR to control food intake, our data show that the activation of these enzymes occurs in the same specific neuronal subtypes. CONCLUSIONS—These findings provide support for the hypothesis that AMPK and mTOR interact in the hypothalamus to regulate feeding during HPD in a leucine-dependent manner.
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Cites
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083
A Randomized Trial of a Low-Carbohydrate Diet for Obesity
Foster, G. D., Wyatt, H. R., Hill, J. O., McGuckin, B. G., Brill, C., Mohammed, B. S., Szapary, P. O., Rader, D. J., Edman, J. S., & Klein, S. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022207 · Cited by 1,794
A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity
Samaha, F. F., Iqbal, N., Seshadri, P., Chicano, K. L., Daily, D. A., McGrory, J., Williams, T., Williams, M., Gracely, E. J., & Stern, L. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022637 · Cited by 1,267
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Metabolic Evidence for Adaptation to a High Protein Diet in Rats
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“These results are in agreement with others (37,38) and can be explained, to some extent, by the reduction in caloric intake, but we also observed increased UCP-1 levels that may reflect an increase in energy expenditure.”
ResultProtein selection by rats adapted to high or moderately low levels of dietary protein
Tews, J. K., Repa, J. J., & Harper, A. E. (1992) · Physiology & Behavior · doi:10.1016/0031-9384(92)90105-b · Cited by 28
Cited by
Watterson, K. R., Bestow, D., Gallagher, J., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2013) · Neurosignals · doi:10.1159/000334144 · Cited by 3,389
Dietary protein, weight loss, and weight maintenance
Westerterp-Plantenga, M. S., Nieuwenhuizen, A., Tomé, D., Soenen, S., & Westerterp, K. R. (2009) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-080508-141056 · Cited by 570
AMPK inhibition in health and disease
Viollet, B., Horman, S., Leclerc, J., Lantier, L., Foretz, M., Billaud, M., Giri, S., & Andreelli, F. (2010) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2010.488215 · Cited by 383
Yang, S.-B., Tien, A.-C., Boddupalli, G., Xu, A. W., Jan, Y. N., & Jan, L. Y. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.043 · Cited by 242
The macronutrients, appetite, and energy intake
Carreiro, A. L., Dhillon, J., Gordon, S., Higgins, K. A., Jacobs, A. G., McArthur, B. M., Redan, B. W., Rivera, R. L., Schmidt, L. R., & Mattes, R. D. (2016) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-121415-112624 · Cited by 159
Metadata
- Authors
- Ropelle, E. R., Pauli, J. R., Fernandes, M. F. A., Rocco, S. A., Marin, R. M., Morari, J., Souza, K. K., Dias, M. M., Gomes-Marcondes, M. C., Gontijo, J. A. R., Franchini, K. G., Velloso, L. A., Saad, M. J. A., & Carvalheira, J. B. C.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2008-03-01
- Volume
- 57
- Issue
- 3
- Pages
- 594-605
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2124359366
- Cited by
- 212
- References
- 8
- FWCI
- 6.00
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- closed
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